PROX1 Promotes Metabolic Adaptation and Fuels Outgrowth of Wnt(high) Metastatic Colon Cancer Cells.

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State: Serval
Version: Final published version
Serval ID
serval:BIB_E480EFD22557
Type
Article: article from journal or magazin.
Collection
Publications
Title
PROX1 Promotes Metabolic Adaptation and Fuels Outgrowth of Wnt(high) Metastatic Colon Cancer Cells.
Journal
Cell Reports
Author(s)
Ragusa S., Cheng J., Ivanov K.I., Zangger N., Ceteci F., Bernier-Latmani J., Milatos S., Joseph J.M., Tercier S., Bouzourene H., Bosman F.T., Letovanec I., Marra G., Gonzalez M., Cammareri P., Sansom O.J., Delorenzi M., Petrova T.V.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
8
Number
6
Pages
1957-1973
Language
english
Abstract
The Wnt pathway is abnormally activated in the majority of colorectal cancers, and significant knowledge has been gained in understanding its role in tumor initiation. However, the mechanisms of metastatic outgrowth in colorectal cancer remain a major challenge. We report that autophagy-dependent metabolic adaptation and survival of metastatic colorectal cancer cells is regulated by the target of oncogenic Wnt signaling, homeobox transcription factor PROX1, expressed by a subpopulation of colon cancer progenitor/stem cells. We identify direct PROX1 target genes and show that repression of a pro-apoptotic member of the BCL2 family, BCL2L15, is important for survival of PROX1(+) cells under metabolic stress. PROX1 inactivation after the establishment of metastases prevented further growth of lesions. Furthermore, autophagy inhibition efficiently targeted metastatic PROX1(+) cells, suggesting a potential therapeutic approach. These data identify PROX1 as a key regulator of the transcriptional network contributing to metastases outgrowth in colorectal cancer.
Pubmed
Web of science
Open Access
Yes
Create date
24/09/2014 9:14
Last modification date
09/05/2019 2:37
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